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The present invention provides compounds of formula I:
whereinR is hydrogen, C1-C6 alkyl, substituted C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 alkylsulfonyl, phenylsulfonyl, substituted phenylsulfonyl, naphthylsulfonyl, benzylsulfonyl, or substituted benzylsulfonyl;R1 is hydrogen or C1-C3 alkyl or where R4 is hydrogen, C1-C6 alkyl, or halo then R1 and R may be taken together to form —CH2—CH2—CH2— or —CH2—CH2—CH2—CH2—;R2 is hydrogen or C1-C6 alkyl;R3 is hydrogen or halo;R4 is hydrogen, C1-C6 alkyl, vinyl, allyl, C2-C6 alkynyl, or halo or when R1 is hydrogen or C1-C3 alkyl then R4 and R may be taken together to form —CH2—CH2—CH2—;X is 1 to 3 substituents independently selected from the group consisting of hydrogen, halo, C1-C6 alkyl, C1-C6 alkoxy, nitro, amino, C1-C6 alkylsulfonylamino, and cyano or X is 5 halo substituents;represents either a single or a double bond; and pharmaceutically acceptable addition salts thereof.
The present invention also provides for novel pharmaceutical compositions, comprising: a compound of the formula I and a pharmaceutically acceptable diluent.
Because the compounds of formula I are antagonists of 5-HT6 receptor, the compounds of formula I are useful for the treatment of a variety of disorders, including: cognitive disorders, age-related cognitive disorder, mild cognitive impairment, mood disorders (including depression, mania, bipolar disorders), psychosis (in particular schizophrenia), anxiety (particularly including generalized anxiety disorder, panic disorder, and obsessive compulsive disorder), idiopathic and drug-induced Parkinson's disease, epilepsy, convulsions, migraine (including migraine headache), substance withdrawal (including, substances such as opiates, nicotine, tobacco products, alcohol, benzodiazepines, cocaine, sedatives, hypnotics, etc.), sleep disorders (including narcolepsy), attention deficit/hyperactivity disorder, conduct disorder, learning disorders, dementia (including Alzheimer's disease and AIDS-induced dementia), Huntington's Chorea, cognitive deficits subsequent to cardiac bypass surgery and grafting, stroke, cerebral ischemia, spinal cord trauma, head trauma, perinatal hypoxia, cardiac arrest, and hypoglycemic neuronal damage, vascular dementia, multi-infarct dementia, amylotrophic lateral sclerosis, and multiple sclerosis, comprising: administering to a patient in need thereof an effective amount of a compound of formula I.
In another embodiment the present invention provides methods of treating disorders associated with the 5-HT6 receptor, comprising: administering to a patient in need thereof an effective amount of a compound of formula I. That is, the present invention provides for the use of a compound of formula I or pharmaceutical composition thereof for the treatment disorders associated with the 5-HT6 receptor.